Hypoparathyroidism
Conditions
Keywords
hypoparathyroidism, XH-02, mRNA drug
Brief summary
XH-02 is an mRNA nucleic acid drug that expresses PTH in the body following intravenous or subcutaneous injection, providing PTH replacement therapy for patients with hypoparathyroidism. Previous clinical studies have demonstrated the safety of subcutaneously administered XH-02 in several patients with hypoparathyroidism and have yielded clear efficacy results. This study aims to further validate the safety and efficacy of subcutaneously injected XH-02 in the treatment of hypoparathyroidism in a expanded cohort.
Interventions
Participants will receive a single dose of XH-02 through subcutaneous injection.
Participants will receive XH-02 via subcutaneous injection daily or every other day, for a total of 5 doses.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single dose: 5 dose groups (40, 60, 80, 120, 160 μg). Multiple doses: 5 dose groups (40, 60, 80, 120, 160 μg), daily or alternate-day dosing.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years, both males and females eligible; 2. History of postoperative chronic HP or autoimmune, genetic, or idiopathic HP for at least 26 weeks. The diagnosis of HP is established based on the presence of inappropriately low serum PTH levels concurrent with hypocalcemia in the past. 3. Poorly controlled or intolerant to conventional treatment (calcium and vitamin D) for hypoparathyroidism; 4. BMI 17-40 kg/m² (inclusive) at screening; 5. If age ≤25 years, radiographic evidence of epiphyseal closure based on X-ray results of the wrist and palm of the non-dominant hand.
Exclusion criteria
1. Impaired PTH response (pseudohypoparathyroidism), characterized by PTH resistance and elevated PTH levels in the presence of hypocalcemia; 2. Allergic constitution, or allergy to the investigational drug or polyethylene glycol (PEG)-based drugs; 3. Any disease other than HP that may affect calcium metabolism, calcium-phosphorus homeostasis, or PTH levels, such as active hyperthyroidism; Paget's disease of bone; severe hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1C \>9%; HbA1C test results from blood samples collected within 12 weeks prior to screening are acceptable); severe and chronic liver or kidney disease; Cushing's syndrome; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobilization; active malignancy (except for low-risk well-differentiated thyroid cancer or non-melanoma skin cancer); active hyperparathyroidism; parathyroid carcinoma occurring within 5 years prior to screening; acromegaly; or multiple endocrine neoplasia; 4. Pregnant or breastfeeding women; 5. Male partners with female partners planning to become pregnant, or partners of childbearing potential who are unwilling to use adequate contraceptive methods during the study period; 6. Patients with high-risk thyroid cancer requiring TSH suppression to \<0.2 mIU/L within 2 years, or those with a history of tumors; 7. Use of loop diuretics, phosphate binders (except calcium supplements), digoxin, lithium, methotrexate, biotin \>30 mcg/day, or systemic corticosteroids (except as replacement therapy); 8. Use of PTH-like drugs (whether commercially available or obtained through participation in clinical trials), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH, or PTH-related protein within 4 weeks prior to screening; 9. Participation in any other interventional trial receiving investigational drugs or devices within 8 weeks prior to screening, or still within 5.5 half-lives of the investigational drug from the trial in which they participated; 10. Presence of uncontrolled hypertension at baseline, or a history of the following cardiovascular or cerebrovascular diseases, including: (1) unstable angina; (2) cardiac arrhythmias requiring medication or severe arrhythmias; (3) myocardial infarction; (4) heart failure class III or higher (NYHA classification), second-degree or higher atrioventricular block; (5) cerebral infarction (excluding lacunar infarction), cerebral hemorrhage, or other such diseases; 11. Increased risk of osteosarcoma, such as having Paget's disease of bone or unexplained elevated alkaline phosphatase, having genetic disorders predisposing to osteosarcoma, or having a prior history of extensive external beam or implant radiation therapy involving bone; 12. Disease processes that adversely affect gastrointestinal absorption, including but not limited to short bowel syndrome, significant small bowel resection, gastric bypass surgery, tropical sprue, active celiac disease, active ulcerative colitis, active Crohn's disease, gastroparesis, and autoimmune regulator gene mutations associated with malabsorption; 13. Any medical or other condition that, in the investigator's judgment, may affect the conduct of the study, interfere with the study results, or increase the risk to the subject/study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (safety) | From the first dose through 30 days after the last dose for non-serious adverse events, and through 3 months after the last dose for severe adverse events. | Adverse events, including serious adverse events. Assessment methods: spontaneous reports; scheduled laboratory tests (hematology, chemistry, C-reactive protein, urinalysis); vital signs (blood pressure, heart rate, respiratory rate, temparature), physical examinations, and electrocardiogram (QTc interval, arrhythmia). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PTH(1-84) (efficacy) | Single dose: Predose (within one hour before dosing) and 4, 8, 12, 18, 24, 30, 36, 48, 60, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 4, 8, 12, 24, 30, 36, 48, 60, and 72 hours after the last dose. | Serum PTH(1-84) |
| PTH (efficacy) | Single dose: Predose (within one hour before dosing) and 4, 8, 12, 18, 24, 30, 36, 48, 60, and 72 hours postdose. | Serum PTH |
| Serum calcium (efficacy) | Single dose: Predose (within one hour before dosing), and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 24, 48, and 72 hours after the last dose. | Serum calcium |
| Serum phosphorus (efficacy) | Single dose: Predose (within one hour before dosing) and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 24, 48, and 72 hours after the last dose. | Serum phosphorus |
| Serum magnesium (efficacy) | Single dose: Predose (within one hour before dosing) and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 24, 48, and 72 hours after the last dose. | Serum magnesium |
| 1, 25-Dihydroxyvitamin D3 (efficacy) | Single dose: Predose (within one hour before dosing) and 24, 48, and 72 hours postdose. Multiple dose: Predose (within one hour before the 1st, 3rd, and 5th dose) and 48 hours and 72 hours after the last dose. | Serum 1, 25-Dihydroxyvitamin D3 |
| 24-hour urine calcium (efficacy) | Single dose: Predose (within 3 days before dosing), and 24, 48, and 72 hours postdose. Multiple dose: Predose (before each dose) and 24, 48, and 72 hours after the last dose. | 24-hour urine calcium (24hUCa) |
| Fractional Excretion of calcium (efficacy) | Single dose: Predose (within one hour before dosing) and 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose (before each dose) and 24, 48, and 72 hours after the last dose. | Fractional Excretion of calcium (FECa) |
Countries
China
Contacts
CONTACTSanXi Ai, Doctor
PRINCIPAL_INVESTIGATORYan Qin
Peking Union Medical College Hospital
Outcome results
None listed